EBV Conference 2008 Guangzhou - Baylor College of Medicine

38 (RegID:1234)
John Arrand
Institution: University of Birmingham
e-mail: j.r.arrand@bham.ac.uk
MOLECULAR GENETIC ANALYSIS OF NASOPHARYNGEAL CARCINOMA
Chunfang Hu, Xiaoyi Chen, Wenbin Wei, Andrew I Bell, John Nicholls, Yunhong Yao, Irène Joab, Paul G
Murray, Lawrence S Young, Chris W Dawson and John R Arrand.
Oralabstract:
MOLECULAR GENETIC ANALYSIS OF NASOPHARYNGEAL CARCINOMA
Chunfang Hu1, Xiaoyi Chen1,2, Wenbin Wei1, Andrew I Bell1, John Nicholls3, Yunhong Yao1,2, Irène
Joab4, Paul G Murray1, Lawrence S Young1, Chris W Dawson1 and John R Arrand1.
1Cancer Research UK Institute for Cancer Studies, School of Cancer Sciences, University of Birmingham,
Birmingham, B15 2TT, U.K.; 2Department of Pathology, Guangdong Medical College, Zhanjiang,
Guangdong, China; 3Department of Pathology, The University of Hong Kong, Hong Kong, China;
4UMR542 Inserm-Université Paris Sud, Hôpital Paul Brousse, Villejuif, France.
Carcinogenesis commonly involves extensive genetic changes and perturbation of cellular gene expression
profiles in tumour cells. Here we describe an analysis of these phenomena in the EBV-associated
neoplasm, nasopharyngeal carcinoma (NPC). Snap-frozen biopsies of EBV-positive NPC were obtained
from Southern China and the Maghreb region of North Africa. Tumour cells and cells from normal
epithelium were obtained by laser-capture microdissection of frozen sections. DNA and total RNA were
extracted, amplified and analysed using Affymetrix 500K SNP arrays and U133Plus2 expression arrays.
Examination of tumour cell DNA revealed that in addition to several extensive regions of chromosomal
gain and loss the high resolution of the SNP arrays identified a number of stretches of relatively short,
discrete copy-number changes. Quantitative PCR was used to validate the array predictions. Loss of
heterozygosity analysis revealed that several tumours exhibited uniparental disomy on some chromosomes
in addition to a number of smaller homozygous regions. Gene expression analysis of tumour cells
compared with normal nasopharyngeal epithelial cells showed that the levels of expression of a large
number of transcripts were significantly altered. Neither the SNP data nor the expression profiles
suggested any substantial geographically-related differences between samples. The expression data were
analysed in the context of genomic copy number changes in the same tumour and for alterations in known
oncogenes and tumour suppressor genes. The data are consistent with our earlier observations of
downregulation of HLA Class I expression in NPC and the induction of RNA polymerase III-related
transcription factors by EBV. In addition we have identified alterations in key signalling pathways that
regulate epithelial cell growth and differentiation. In agreement with earlier studies we observe alterations
in the canonical and non-canonical Wnt signalling pathways and in addition have identified alterations in
the TGF-beta pathway.
EBV Conference 2008 Guangzhou
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